Tetrafunctional bacteriophage

A recombinant targeted bacteriophage for expressing a transgene in a target cell transduced with the bacteriophage, the bacteriophage comprising:

• (i) a first nucleic acid sequence encoding a pIII capsid minor coat protein fused to a cell-targeting ligand for enabling delivery of the bacteriophage to a mammalian target cell;
• (ii) a second nucleic acid sequence encoding at least one wild type pVIII capsid major coat protein for supporting bacteriophage assembly, fused to a foreign peptide of less than ten amino acids;
• (iii) a third nucleic acid sequence encoding a recombinant pVIII capsid major coat protein, which differs in nucleotide sequences from the nucleotide sequence encoding the wild-type pVIII capsid major coat protein, fused to a foreign peptide of more than ten amino acids, wherein the foreign peptide which is displayed on the pVIII capsid major coat protein comprises an endosome escape peptide (EEP), wherein the EEP is displayed on the recombinant pVIII capsid major coat protein;
• and wherein the endosome escape peptide is H5WYG peptide as set forth in SEQ ID NO:
• 9;
• and
• (iv) a mammalian transgene cassette which encodes a protein which exerts a biological effect on the target cell.